Programme et résumés de la 9e réunion du réseau national

Pro
g
ré
s
22 - 23
Centre c
o
A
gence nationale de recherches sur le
g
ramme
et
et
s
umés
janvier 2009
o
ngrès UICP, Paris
sida et les hépatites virales

1

2
SOMMAIRE
RECEPTORCOMPLEMENTATIONANDTARGETEDMUTAGENESISREVEALSR‐BIASANESSENTIALHCVCELL
ENTRYFACTORANDFUNCTIONALLYIMPLYITSINTRA‐ANDEXTRA‐CELLULARDOMAINS
(M.DREUX)..................................................................................................................................................10
SCAVENGERRECEPTORCLASSBTYPEIANDSERUM‐DERIVEDHEPATITISCVIRUSINFECTIONOFPRIMARY
NORMALHUMANHEPATOCYTES
(C.GONDEAU)..............................................................................................................................................13
IDENTIFICATIONDEDEUXKINASESCELLULAIRESIMPLIQUEESALAFOISDANSL’ENTREEETLAREPLICATION
DUVHC
(M.TROTARD)..............................................................................................................................................14
ROLEDESGLYCANESDANSLESFONCTIONSDEPROTEINESD’ENVELOPPEDUVHC
(F.HELLE).....................................................................................................................................................15
HEPATITISCVIRUSENTRYISAVIABLETARGETFORPREVENTIONOFRE‐INFECTIONINLIVER
TRANSPLANTATION
(S.FAFI‐KREMER).........................................................................................................................................16
CHARACTERIZATIONOFTHEMEMBRANEFUSIONPROPERTIESOFCELLCULTURE‐PRODUCEDHEPATITISC
VIRUSPARTICLES
(E‐I.PECHEUR)..............................................................................................................................................17
ANALYSEDESDETERMINANTSD’ENTREEVIRALEPORTESPARLESPROTEINESD’ENVELOPPEDUVIRUSDE
L’HEPATITEB
(Y.LEDUFF)..................................................................................................................................................18
L’ETABLISSEMENTDEL’INFECTION,LAREPLICATIONETLAPROPAGATIONDUVIRUSDEL’HEPATITEC
SERIQUE(HCVSP)DEPENDENTDEL’ETATDEPROLIFERATION/DIFFERENCIATIONDESCELLULESHEPARG
HUMAINESPROGENITRICESDUFOIE
(N.NDONGO)...............................................................................................................................................19
ETUDEULTRASTRUCTURALEETBIOCHIMIQUEDESMEMBRANESCELLULAIRESASSOCIEESAUXCOMPLEXES
DEREPLICATIONDUVHC
(P.FERRARIS)...............................................................................................................................................20
GBF1UNNOUVEAUFACTEURCELLULAIRENECESSAIREPOURLAREPLICATIONDUVIRUSDEL’HEPATITEC
(L.GOUESLAIN)............................................................................................................................................21
INVESTIGATINGTHEROLEOFTHEN‐TERMINALBASICREGIONOFTHEHEPATITISCVIRUSCOREPROTEININ
VIRALREPLICATION
(Z.MAKOWSKA)...........................................................................................................................................22
STRUCTURESCRISTALLOGRAPHIQUESDEPOLYMERASESVIRALES:UNCONTEXTEPOURLACOMPREHENSION
DELAREPLICATIONDUVIRUSDEL’HEPATITEC
(S.BRESSANELLI)..........................................................................................................................................23
CARACTERISATIONSTRUCTURALEDESCHANGEMENTSDECONFORMATIONDELAPOLYMERASEDUVIRUS
DEL’HEPATITEC:ROLEDUCONNECTEURAL’ANCRETRANSMEMBRANAIRE
(D.HARRUS).................................................................................................................................................24
HEPATITISCVIRUSNS5APROTEINISASUBSTRATEFORTHEPEPTIDYL‐PROLYLCIS/TRANSISOMERASE
ACTIVITYOFCYCLOPHILINSAANDB
(X.HANOULLE).............................................................................................................................................25
ROLEDEHBXDANSL’INFECTIONPARLEVIRUSDEL’HEPATITEBDELALIGNEEHEPATOCYTAIREHEPARG
(O.HANTZ)...................................................................................................................................................26

3
TRANSACTIVATIONOFTHEHEPATITISBVIRUSCOREPROMOTERBYTHENUCLEARRECEPTORFXRΑ
(C.RAMIERE)................................................................................................................................................27
LEVIRUSDEL’HEPATITECINDUITLAFIBROSEHEPATIQUESANSINFLAMMATIONCHEZDESSOURIS
TRANSGENIQUESEXPRIMANTLATOTALITEDUCADREOUVERTDELECTUREVIRAL
(P.CHOUTEAU)............................................................................................................................................28
HEPATITISCVIRUSMODULATESHEPATOCYTEAPOPTOSISBYTARGETINGBID
(U.HIBNER)..................................................................................................................................................30
ANALYSEULTRASTRUCTURALEETQUANTITATIVEDESREGROUPEMENTSDEGOUTTELETTESLIPIDIQUES
INDUITSPARLAPROTÉINEDECOREDUVHC
(M.DEPLA)...................................................................................................................................................31
N‐TERMINALUBIQUITINATIONOFHEPATITISBVIRUSXPROTEIN
(S.BENHENDA).............................................................................................................................................33
LEROLEDURETROTRANSPORTDURETICULUMENDOPLASMIQUEVERSLECYTOPLASMEDELAPROTEINE
PRECOREDUVIRUSDEL’HEPATITEBHUMAINE
(M.DURIEZ).................................................................................................................................................34
HEPATITISCVIRUSNON‐STRUCTURALPROTEIN2DISTURBSTHESECRETORYPATHWAYANDITSEFFECTIS
COMPENSATEDBYTHEVIRALENVELOPEPROTEINS
(N.CALLENS)................................................................................................................................................35
HEPATITISCVIRUSINFECTIONPROTEINNETWORK
(B.DECHASSEY)...........................................................................................................................................36
INHIBITIONDRASTIQUEDESECRETIONDESHEPADNAVIRUSPARUNPEPTIDEPERMEABILISANT
(F.ABDUL)....................................................................................................................................................37
CARACTERISATIOND’UNENOUVELLEMUTATIONDERESISTANCE(V36C)CHEZUNPATIENTTRAITEAVECUNE
TRITHERAPIEDETELAPREVIR,D’IFN‐ALPHA2APEGYLEETDERIBAVIRINE
(L.BARBOTTE)..............................................................................................................................................38
EFFETANTIVIRALDUBAY41‐4109DANSUNMODELEANIMALHUMANISEETINFECTEPARLEVHB:LASOURIS
ALB‐UPA/SCID
(N.BREZILLON).............................................................................................................................................40
REACTIVATIONSOUSL’ASSOCIATIONFLUTICASONE‐RITONAVIRD'UNEINFECTIONAVHBOCCULTECHEZUN
PATIENTANTI‐HBS+ETCO‐INFECTEPARLEVIH
(A.KAY)........................................................................................................................................................41
NOUVELLESTRATEGIEANTIVIRALE:DESARNNEGATIFSCONTRELEVHC
(J.BITARD)...................................................................................................................................................43
HEPATITISCVIRUSIMPAIRSPLASMACYTOIDDENDRITICCELL‐ASSOCIATEDPRODUCTIONOFINTERFERON
ALPHA
(I.HIRSCH)....................................................................................................................................................44
UPTAKEANDTRAFFICKINGOFCELLCULTURE‐DERIVEDHEPATITISCVIRUS(HCVCC)INHUMAN
PLASMACYTOIDDENDRITICCELLS
(M.LAMBOTIN)............................................................................................................................................45
REPONSENEUTRALISANTEHUMORALECONTRELEVHCLORSDELACOINFECTIONPARLEVIHETDELA
TRANSPLANTATIONHEPATIQUE
(G.MAURIN)................................................................................................................................................47
CRITICALROLEOFINTRA‐HEPATICCD4+CD25+FOXP3+CELLSINHCVINFECTEDPATIENTS
(E.JOUVIN‐MARCHE)....................................................................................................................................49
ÉTUDEDEL’ENCAPSIDATIONDUGENOMEDUVHCPARMESUREDEL’INTERACTIONENTRELAPROTEINE
COREETL’ARNVIRALAUMOYEND’UNVECTEURLENTIVIRALEXVIVO
(E.PIVER).....................................................................................................................................................50

4
L’IRESDUVHCINTERAGITAVECLEMOTIFDERECONNAISSANCEMRRDELASOUSUNITEBDUFACTEUR
D’INITIATIONEIF3
(J.PERARD)..................................................................................................................................................51
ETUDESTRUCTURALEDELAPOLYMERASEMEMBRANAIREDUVIRUSDEL’HEPATITEC.PRODUCTIONET
PURIFICATIONDELAPOLYMERASEENTIERE
(C.CAILLET‐SAGUY)......................................................................................................................................52
DESCRIPTIOND’UNEINSERTIONV3‐LIKEDANSLEGENENS5ADUVIRUSDEL’HEPATITECDEGENOTYPE1B
CHEZDESPATIENTSCHRONIQUEMENTINFECTES
(O.PETSARIS)...............................................................................................................................................53
EFFETSFONCTIONNELSDESFORMESSECRETEESDUPRODUITDUGENEPRECDUVHBSURLESLYMPHOCYTES
T
(M.PURVINA)..............................................................................................................................................55
ETUDEDESREPONSESIMMUNITAIRESINDUITESPARLEVIRUSDEL’HEPATITEC:UTILISATIONDEPUCESA
PEPTIDESETAPROTEINES
(S.CORTES)..................................................................................................................................................56
EFFETINHIBITEURETCALCINEURINEINDEPENDANTDELACYCLOSPORINEASURLESCELLULEST
REGULATRICESCD4+CD25+HUMAINESINVITRO
(C.MIROUX).................................................................................................................................................58
POTENTIALISATIONDELARÉPONSEHUMORALENEUTRALISANTEDUVACCINÀADNDIRIGÉCONTRELE
DHBVPARCO‐ADMINISTRATIONDEGÈNESCODANTPOURDESCYTOKINES
(F.SAADE)....................................................................................................................................................60